DESCRIPTION (Adapted from the Investigator's Abstract) The long-term objective of this proposal is to understand the cellular and biochemical basis of long-term memory storage, using the storage of odor memories in the olfactory system of a terrestrial mollusk as a model system. We will test a specific cellular and biophysical model for how the major central site of odor information processing in the terrestrial slug Limax maximus forms odor memories as spatially segregated bands of neurons. The odor memory storage site, the procerebral (PC) lobe, is analogous to the mammalian olfactory bulb. The hypothesis to be tested is that olfactory memories are identified by odor learning-dependent uptake of a highly fluorescent dye, Lucifer yellow, by groups of neurons in the PC lobe. Learning-dependent dye uptake identifies the neurons involved in storing the odor memory for detailed biophysical and biochemical analysis. The specific aims of the proposed work will test several predictions of the hypothesis that the learning-dependent dye labeling identifies neurons storing an odor memory. The following specific experimental questions will be addressed; 1. If the slug is denied access to the dye-labeled neurons in the PC lobe after odor training, does it act naive in a behavioral test of odor memory function? 2. Does the spacing between two dye-labeled bands produced by learning about two odors predict the ability to discriminate between the two learned odors? 3. Are the dye labeled neurons present after odor training selectively activated by stimulation with the trained odor? 4.Do drugs which disrupt normal dynamics of neuronal activity in the PC lobe also degrade odor learning and odor discrimination? The computational model which leads to the specific experimental tests listed in the specific aims will be expanded to incorporate more specific details of the cellular biophysics and neuron connectivity in the PC lobe. We also will study the cellular mechanism of learning-dependent dye uptake to develop this memory localization tool for use in mammalian brain. The conserved nature of biochemical memory mechanisms and system design principles in olfactory systems makes it very likely that mechanisms for odor memory storage in the molluscan nervous system will have direct relevance to the mammalian nervous system. The results of this work will contribute to efforts to develop pharmacological interventions for clinical syndromes in which loss of memory function is a major component, such as mental retardation and Alzheimers disease.